Amyloid P peptide (AD) immunization has emerged as a novel therapeutic strategy for the treatment or prevention of Alzheimer's disease (AD). In mice, the efficacy of this approach appears to be dependent on the ability to achieve a high level of anti-Ap antibody (Ab) in response to immunization with fibrillar AD or to deliver a large quantity of certain anti-AD Abs by passive immunization. In humans, there are concerns that the potential efficacy of AD immunization may be compromised due to a blunted or absent immune response to AD. One way to overcome this would be to develop humanized anti-Ap antibodies for passive immunization, however, production of large amounts of recombinant humanized antibodies is not trivial and only a small fraction of candidate therapeutic antibodies have been developed for large scale testing in humans. As an alternative approach we propose to explore recombinant adenoviral (Ad) vectors (AdVs) for in vivo production of anti-AD antibodies, and then to test these in an APP transgenic mouse model in which AD vaccination has been shown to have efficacy. In addition, we will evaluate the effects of peripheral versus CNS expression of the anti-Ap antibodies in two ways. We will compare direct injection of the recombinant anti-AD AdV into the brain versus peripheral administration and also attempt to develop AdVs tropic for the CNS that can be administered systemically but target expression to the CNS.